Structural equation modeling approach between salience network dysfunction, depressed mood, and subjective quality of life in schizophrenia: an ICA resting-state fMRI study

Figures & data

Table 1 Demographic and clinical parameters of the healthy control and patient groups

Characteristics	Schizophrenia (mean ± SD)	Controls (mean ± SD)	p-value
Number (male/female)	21 (11/10)	21 (11/10)	nsa
Age (years)	42.3 ± 10.2	42.7 ± 10.6	nsb
Education level (years)	14.3 ± 1.8	15 ± 2.3	nsc
Handedness (right/left)	21/0	21/0
IQ (WAIS-III short form)	83.6 ± 14.8	106.0 ±15.8	<0.001b
SQLS
Psychosocial	24.5 ± 13.5	17.2 ± 7.3	<0.05b
Motivation/energy	13.4 ± 5.0	11.0 ± 4.0	nsb
Symptom/side effects	9.2 ± 9.6	5.9 ± 4.8	nsc
Duration of illness (years)	15.9 ± 8.4
Drug (mg/day, CPZ equivalentd)	380.6 ± 264.3
PANSS
Positive	11.9 ± 3.5
Negative	15.7 ± 4.1
General	29.0 ± 5.9
CDSS total score	3.1 ± 3.3
BACS composite score	−1.26 ± 0.84
DIEPSS total score	1.5 ± 2.1

Notes:

a Chi-square test;

b Student’s t-test;

c Mann–Whitney U-test;

d CPZ equivalents were calculated according to Inagaki and Inada.⁷⁵

Abbreviations: BACS, Brief Assessment of Cognition in Schizophrenia; CDSS, Calgary Depression Scale for Schizophrenia; CPZ, chlorpromazine; DIEPSS, Drug Induced Extra-Pyramidal Symptoms Scale; PANSS, Positive and Negative Syndrome Scale; SQLS, Schizophrenia Quality of Life Scale; WAIS-III, Wechsler Adult Intelligence Scale-III; ns, not significant.

Figure 1 The ICA analysis results.

Notes: Spatial maps are shown based on t-statistics with significance defined as FWE-corrected p < 0.05. This RSN map was highly correlated with the salience network,⁴⁹ which includes the insular cortex and anterior cingulate cortex. The color bar represents t-values.
Abbreviations: FWE, family-wise error; ICA, independent component analysis; RSN, resting-state network.

Figure 2 Group comparisons of SN FC (patients versus controls).

Notes: (A) Compared to the controls, the patients exhibited significantly lower SN FC in the right pallidum ([x y z] = [22 −2 −6]). (B) Mean right pallidum FC values (Z-score) for patients and controls. The error bars indicate standard errors.
Abbreviations: FC, functional connectivity; SN, salience network; SC, schizophrenia; HC, healthy control.

Table 2 Regions showing significant decreased salience network functional connectivity in patients with schizophrenia (n = 21) compared to controls (n = 21)

Region	MNI [x y z] (mm)	Voxel number	t-value	Cluster-level (pFWE-corr)	Voxel-level (pFWE-corr)
Right pallidum	[22 −2 −6]	245	5.8	0.010	0.027

Note: The table lists the region’s MNI coordinate, number of voxels (cluster size), peak voxel t-value, cluster-level p-value, and the voxel-level p-value.

Abbreviations: FWE-corr, family-wise error corrected; MNI, Montreal Neurological Institute.

Table 3 Correlation coefficients between right pallidum FC, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores in patients with schizophrenia (n = 21)

Variables	FC of right pallidum	PANSS positive	PANSS negative	CDSS	BACS	PS of SQLS	Drug	DIEPSS
FC of right pallidum	1
PANSS positive	−0.257a	1
PANSS negative	−0.134a	0.746a,**	1
CDSS	−0.509b	0.348b	0.171b	1
BACS	−0.024a	−0.082a	−0.190a	−0.187b	1
PS of SQLS	−0.275a	0.293a	0.230a	0.785b,***	−0.244a	1
Drug	−0.291b	0.351b	0.143b	0.548b	0.005b	0.597b	1
DIEPSS	−0.107b	0.529b	0.384b	−0.047b	0.351b	−0.011b	−0.187b	1

Notes:

a Pearson correlation;

b Spearman correlation;

** p < 0.005;

*** p < 0.001.

Abbreviations: BACS, Brief Assessment of Cognition in Schizophrenia; CDSS, Calgary Depression Scale for Schizophrenia; DIEPSS, Drug Induced Extra-Pyramidal Symptoms Scale; FC, functional connectivity; PANSS, Positive and Negative Syndrome Scale; PS, psychosocial; SQLS, Schizophrenia Quality of Life Scale.

Figure 3 SEM results of the best model.

Notes: Model 3 exhibited the best fit (chi-squared p-value = 0.9, RMSEA < 0.001, CFI = 1.00, and SRMR = 0.020). The SEM revealed significant and moderate-to-strong associations between (1) right pallidum FC and CDSS total scores (path coefficient = −0.43, p-value < 0.05) and between (2) CDSS total scores and SQLS psychosocial subscale scores (path coefficient = 0.76, p-value < 0.001); *p < 0.05, ***p < 0.001.
Abbreviations: CFI, comparative fit index; FC, functional connectivity; CDSS, Calgary Depression Scale for Schizophrenia; RMSEA, root mean square error of approximation; PS, psychosocial; SEM, structural equation modeling; SN, salience network; SQLS, schizophrenia Quality of Life Scale; SRMR, standardized root mean square residuals.

Table 4 Fit measures for the structural equation models

Models	Fit index							Estimates of coefficients
	p-value (chi-square)	RMSEA	CFI	TLI	SRMR	AIC	BIC	Regression			Estimates	SE	p-value
Model 1	0.49	0.017	1.00	0.99	0.082	180.40	184.58	Positive	~	Z-score	−0.26	0.22	0.24
								PS of SQLS	~	Positive	0.29	0.24	0.23
Model 2	0.36	0.14	<0.001	14.88	0.10	182.19	186.37	Negative	~	Z-score	−0.13	0.20	0.49
								PS of SQLS	~	Negative	0.23	0.22	0.29
Model 3	0.9	<0.001	1.00	1.13	0.020	161.29	165.47	CDSS	~	Z-score	−0.43	0.19	0.02*
								PS of SQLS	~	CDSS	0.76	0.16	<0.001***
Model 4	0.3	0.20	<0.001	−17.36	0.12	182.42	186.60	BACS	~	Z-score	−0.02	0.21	0.91
								PS of SQLS	~	BACS	−0.24	0.22	0.27
Model 5	–	–	–	–	–	181.39	186.62	PS of SQLS	~	Z-score	−0.21	0.20	0.27
								Positive	~	Z-score	−0.26	0.23	0.25
								PS of SQLS	~	Positive	0.24	0.24	0.32
Model 6	–	–	–	–	–	182.80	188.02	PS of SQLS	~	Z-score	−0.25	0.20	0.21
								Negative	~	Z-score	−0.13	0.20	0.50
								PS of SQLS	~	Negative	0.20	0.20	0.33
Model 7	–	–	–	–	–	163.15	168.37	PS of SQLS	~	Z-score	0.06	0.14	0.66
								CDSS	~	Z-score	−0.43	0.18	0.02*
								PS of SQLS	~	CDSS	0.79	0.20	<0.001***
Model 8	–	–	–	–	–	182.58	187.80	PS of SQLS	~	Z-score	−0.28	0.22	0.20
								BACS	~	Z-score	−0.02	0.21	0.91
								PS of SQLS	~	BACS	−0.25	0.22	0.26

Notes:

* p < 0.05;

*** p < 0.001. “–” indicated as not available.

Abbreviations: AIC, Akaike’s Information Criterion; BACS, Brief Assessment of Cognition in Schizophrenia; BIC, Bayesian Information Criterion; CDSS, Calgary Depression Scale for Schizophrenia; CFI, comparative fit index; PS, psychosocial; RMSEA, root mean square error of approximation; SE, standard error; SQLS, Schizophrenia Quality of Life Scale; SRMR, standardized root mean square residuals; TLI, Tucker-Levis index.

Figure S1 Model specification.

Note: Based on previous studies,^1–6 we developed the hypotheses and made eight models for the purpose of SEM.

Abbreviations: QOL, quality of life; SN, salience network; SEM, structural equation modeling.

Figure S2 Comparison of connectivity maps for patients and controls across three RSNs (DMN, CEN, and SN).

Notes: Spatial maps are shown based on t-statistics with significance defined as FWE-corrected p < 0.05. Each RSN map was highly correlated with the RSN template (DMN, CEN, and SN),⁷ respectively. The groups had similar DMN and CEN expressions. We could not find any significant group differences in DMN nor CEN.

Abbreviations: CEN, central executive network; DMN, default mode network; RSN, resting-state network; SN, salience network; FWE, family-wise error.

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