Structural and functional brain abnormalities in drug-naive, first-episode, and chronic patients with schizophrenia: a multimodal MRI study

Figures & data

Figure 1 Flow diagram of the classification approach employed in this study.

Notes: The classification schematic flow using the combined sMRI and rs-fMRI features. In detail, 1,024 features from GMV, 1,024 features from ReHo, 1,024 features from ALFF, and 1,024 features from DC concatenated into a 4,096-dimensional vector. SVM-RFE and 10-fold cross validation were applied for feature selection and classifier training.
Abbreviations: AAL, automated anatomical labeling; ALFF, amplitude of low-frequency fluctuation; DC, degree centrality; GMV, gray matter volume; rs-fMRI, resting-state functional magnetic resonance imaging; RFE, recursive feature elimination; ReHo, regional homogeneity; sMRI, structural magnetic resonance imaging; SVM, support vector machine.

Table 1 Demographic and clinical characteristics

	FESZ patients (n=43)	NC (n=56)	CSZ patients (n=39)	F value (χ^2)	P-value
Age (years)	26.42±8.02	25.07±5.85	29.97±6.97	5.94	0.004a
Gender (F:M)	15:28	23:33	15:24	0.39b	0.82b
Education (years) TBV (mm^3)	10.37±3.29 1,193.27±111.65	12.14±2.42 1,203.59±108.70	11.44±2.76 1,154.97±120.88	4.84 2.224	0.009c 0.14
PANSS-PScore PANSS-NScore	25.21±3.93 21.42±7.84	7.05±0.30 8.79±2.70	23.39±3.31 22.39±6.40	632.15 85.18	<0.0001a,c <0.0001a,c
PANSS-GScore PANSS-TScore	40.49±9.21 87.12±18.09	17.18±2.34 33.02±4.74	39.13±6.82 84.897±12.31	205.38 305.07	<0.0001a,c <0.0001a,c

Notes: Values are represented as the mean±SD. The comparisons of clinical and demographic characteristics among the three groups (FESZ, NC, and CSZ) were performed using a separate one-way ANOVA. Post hoc pairwise comparisons were then performed using two sample t-test. Statistical significance was set at P<0.05.

a Post hoc paired comparisons showed significant group differences between CSZ versus NC.

b For the gender distribution among the three groups, P-value was obtained using χ² test.

c Post hoc paired comparisons showed significant group differences between FESZ versus NC. Post hoc paired comparisons showed significant group differences between FESZ versus CSZ. Abbreviations: CSZ, chronic schizophrenia; F, female; FESZ, first-episode drug-naive schizophrenia; GScore, general score; M, male; NC, normal control; NScore, negative syndrome score; PANSS, Positive and Negative Syndrome Scale; PScore, positive syndrome score; TBV, total brain volume; TScore, total syndrome score.

Figure 2 Between-group differences in the regional GMV (A), ReHo (B), ALFF (C), and DC (D).

Notes: (I) The warm color means that FESZ patients’ structural brain changes and functional activities were significantly higher than NCs, and the cool color means the opposite. (II) The warm color means that the CSZ patients’ structural brain changes and functional activities were significantly higher than NCs, and the cool color means the opposite. (III) The warm color means that the FESZ patients’ structural brain changes and functional activities were significantly higher than CSZ patients’ structural brain changes and functional activities, and the cool color means the opposite. The 3D maps were made using BrainNet Viewer (http://www.nitrc.org/projects/bnv/), and the 3D perspective drawing was made using ParaView (https://www.paraview.org/).
Abbreviations: ALFF, amplitude of low-frequency fluctuation; CSZ, chronic schizophrenia; DC, degree centrality; FESZ, first-episode drug-naive schizophrenia; GMV, gray matter volume; NC, normal control; ReHo, regional homogeneity.

Table 2 Classification performances

	Sensitivity (%)	Specificity (%)	Accuracy (%)	AUC
FESZ/NC	72.09	85.71	79.80	0.88
CSZ/NC	71.79	91.07	83.16	0.92
FESZ/CSZ	88.37	74.36	81.71	0.87

Abbreviations: AUC, area under the ROC curve; CSZ, chronic schizophrenia; FESZ, first-episode drug-naive schizophrenia; NC, normal control; ROC, receiver operating characteristic.

Figure 3 Classification results.

Notes: The classification between the FESZ and NC groups (blue line), the classification between the CSZ and NC groups (red line), and the classification between the FESZ and CSZ groups (black line). The areas under the ROC curve of the three classifiers were 0.88, 0.92, and 0.87, respectively.
Abbreviations: CSZ, chronic schizophrenia; FESZ, first-episode drug-naive schizophrenia; NC, normal control; ROC, receiver operating characteristic.

Table S1 Significant differences in GMV among three groups

	Anatomical region	Hemisphere	Cluster size (voxels)	MNI coordinates (mm)			t value
				X	Y	Z
FESZ>NC
1	Postcentral gyrus	L	151	−30	−36	58	2.960
2	Cuneus	R	142	28	−72	18	3.039
FESZ<NC
3	Fusiform gyrus	R	151	38	−68	−20	3.022
4	Middle occipital gyrus	L	150	−38	−92	10	2.859
5	Posterior cingulate	L	150	−2	−50	10	3.102
6	Parahippocampal gyrus	L	115	−16	−30	−20	3.179
SZ>NC
7	Thalamus	L	296	0	−14	10	3.093
8	Postcentral gyrus	L	150	−20	−46	64	3.591
9	Precuneus	R	142	28	−72	18	2.886
SZ<NC
10	Superior temporal gyrus	L	151	−50	20	−26	3.348
11	Lingual gyrus	R	150	12	−78	−14	3.222
12	Middle occipital gyrus	L	150	−38	−72	−10	3.047
13	Middle occipital gyrus	R	150	42	−92	0	3.511
14	Posterior cingulate	L	301	8	−46	14	3.551
15	Cingulate gyrus	L	151	−4	20	30	3.079
16	Cingulate gyrus	R	151	16	−30	38	3.290
17	Superior frontal gyrus	L	151	−8	0	50	3.415
FESZ>SZ
18	Superior temporal gyrus	L	151	−50	20	−26	2.908
19	Medial frontal gyrus	R	150	14	52	4	2.879

Abbreviations: FESZ, first-episode drug-naive schizophrenia; GMV, gray matter volume; L, left; MNI, Montreal Neurological Institute; NC, normal control; R, right; SZ, schizophrenia.

Table S2 Significant differences in ReHo among three groups

	Anatomical region	Hemisphere	Cluster size (voxels)	MNI coordinates (mm)			t value
				X	Y	Z
FESZ>NC
1	Fusiform	L	151	−30	−10	−46	2.936
2	Temporal pole	R	151	50	22	−34	3.647
3	Putamen	L	300	−12	16	−26	4.222
4	Parahippocampal gyrus	R	752	34	−2	−24	3.502
5	Superior temporal gyrus	R	451	68	−46	4	3.861
6	Postcentral gyrus	R	151	66	−26	24	3.065
7	Middle frontal gyrus	R	150	46	34	30	3.018
8	Inferior parietal lobe	L	451	−48	−54	34	4.226
9	Middle occipital gyrus	L	151	−20	−90	6	−2.910
SZ>NC
10	Middle temporal gyrus	R	151	36	6	−44	3.128
11	Parahippocampal gyrus	R	151	30	−20	−32	3.004
12	Precuneus	Both	150	0	−66	30	3.018
13	Cingulate gyrus	L	151	0	−32	30	3.180
14	Inferior parietal lobule	L	151	−40	−58	34	3.021
15	Precuneus	L	151	−8	−56	58	3.401
SZ<NC
16	Superior temporal gyrus	L	151	−54	−6	−8	2.998
17	Precentral gyrus	L	604	−66	−6	14	3.953
18	Precentral gyrus	R	299	56	−8	24	3.366
FESZ>SZ
19	Superior temporal gyrus	L	302	−66	−6	14	3.354
20	Precentral gyrus	L	602	−58	−18	22	3.810
21	Postcentral gyrus	R	151	62	−26	48	2.890
22	Postcentral gyrus	L	150	−44	−26	52	3.103

Abbreviations: FESZ, first-episode drug-naive schizophrenia; L, left; MNI, Montreal Neurological Institute; NC, normal control; R, right; ReHo, regional homogeneity; SZ, schizophrenia.

Table S3 Significant differences in ALFF among three groups

	Anatomical region	Hemisphere	Cluster size (voxels)	MNI coordinates (mm)			t value
				X	Y	Z
FESZ>NC
1	Middle temporal gyrus	R	1,807	48	−2	−48	3.929
2	Middle temporal gyrus	L	302	−58	−4	−36	3.230
3	Inferior frontal gyrus	L	902	−12	16	−26	3.557
4	Inferior frontal gyrus	R	302	22	12	−22	3.312
5	Superior temporal gyrus	L	302	−56	−24	−8	3.520
6	Superior temporal gyrus	R	453	68	−46	4	3.261
7	Superior frontal gyrus	L	150	−12	56	26	3.945
8	Middle frontal gyrus	R	150	46	34	30	3.818
FESZ<NC
9	Fusiform gyrus	R	422	30	−70	−10	3.543
10	Posterior cingulate	L	758	−2	−50	10	3.546
SZ>NC
11	Superior temporal gyrus	L	600	−32	10	−34	3.280
12	Temporal pole	R	151	36	6	−44	3.156
13	Caudate	R	151	10	26	−22	3.023
14	Middle orbital frontal cortex	L	151	−46	36	−18	3.170
15	Middle frontal gyrus	R	151	52	50	−8	2.969
16	Middle frontal gyrus	L	151	−38	48	−6	3.300
17	Superior frontal gyrus	L	150	−12	56	26	3.544
SZ<NC
18	Middle occipital gyrus	R	150	52	−60	−22	2.965
19	Middle occipital gyrus	L	1,056	−36	−78	−16	3.819
FESZ>SZ
20	Middle occipital gyrus	L	1,056	−36	−78	−16	3.694
21	Superior temporal gyrus	L	151	−56	−24	−8	3.611
22	Postcentral gyrus	L	301	−66	−18	28	3.340
23	Postcentral gyrus	R	150	46	−22	36	3.282

Abbreviations: ALFF, amplitude of low-frequency fluctuation; FESZ, first-episode drug-naive schizophrenia; L, left; MNI, Montreal Neurological Institute; NC, normal control; R, right; SZ, schizophrenia.

Table S4 Significant differences in DC among three groups

	Anatomical region	Hemisphere	Cluster size (voxels)	MNI coordinates (mm)			t value
				X	Y	Z
FESZ<NC
1	Fusiform	R	302	30	−8	−46	3.376
2	Medial frontal gyrus	R	451	8	18	−26	3.340
3	Parahippocampal gyrus	R	151	20	−38	−18	2.975
4	Calcarine	R	247	34	−64	−12	3.944
5	Inferior frontal gyrus	R	151	56	26	−8	3.666
6	Precuneus	R	297	28	−72	18	3.103
7	Precuneus	L	150	−2	−44	64	2.863
SZ<NC
8	Parahippocampal gyrus	R	151	18	14	−40	3.398
9	Fusiform	L	151	−40	−50	−24	2.897
10	Middle occipital gyrus	L	453	−54	−70	−16	3.561
11	Superior temporal gyrus	R	905	38	0	−12	3.502
12	Superior temporal gyrus	L	452	−66	−6	14	3.073
13	Middle temporal gyrus	L	151	−60	−66	2	3.241
14	Cuneus	L	150	−14	−62	6	2.913
15	Middle frontal gyrus	R	903	36	16	34	3.756
16	Precuneus	Both	150	0	−76	14	2.867
17	Precentral gyrus	L	441	−62	−6	20	3.073
18	Middle frontal gyrus	L	151	−32	4	38	3.713
19	Medial frontal gyrus	L	300	2	−14	60	3.358
20	Paracentral lobe	Both	150	0	−40	66	3.109
FESZ>SZ
21	Superior temporal gyrus	R	151	46	−10	0	2.907

Abbreviations: DC, degree centrality; FESZ, first-episode drug-naive schizophrenia; L, left; MNI, Montreal Neurological Institute; NC, normal control; R, right; SZ, schizophrenia.