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

Abstract

Purpose

Quality of life (QOL) is an important clinical outcome for patients with schizophrenia, and recent studies have focused on subjective QOL. We evaluated the causal relationship between psychosocial aspect of subjective QOL, symptoms, cognitive functions, and salience network (SN) dysfunction in schizophrenia using structural equation modeling (SEM).

Patients and methods

We performed a cross-sectional study of 21 patients with symptomatically stabilized schizophrenia and 21 age-, sex-, and education level-matched healthy controls who underwent resting-state functional magnetic resonance imaging. We evaluated SN dysfunction in schizophrenia using independent component analysis (ICA). We rated participant psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied SEM to examine the relationships between SN dysfunction, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores.

Results

In second-level analysis after group ICA, patient group had significant lower right pallidum functional connectivity (FC) within the SN than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 −2 −6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good fit for an SEM model in which SN dysfunction causes depressed mood, which in turn determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] = 1.00, and standardized root mean square residual [SRMR]= 0.020).

Conclusion

We found a continuous process by which SN dysfunction causes depressed moods that determine psychosocial aspect of subjective QOL in schizophrenia. This is the first report that offers a unified explanation of functional neuroimaging, symptoms, and outcomes. Future studies combining neuroimaging techniques and clinical assessments would elucidate schizophrenia’s pathogenesis.

Keywords:

• depressed mood
• salience network
• schizophrenia
• structural equation modeling
• subjective quality of life
• resting-state fMRI

Supplementary materials

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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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (TO). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report and the decision to submit it for publication.

We would like to thank the staff at Tokushima University Hospital for support with fMRI data acquisition. We would like to thank Editage (www.editage.jp) for English language editing. We also thank the participants for their involvement and dedication to this study.

Author contributions

M Ohta and M Nakataki designed the study. M Nakataki and T Ohmori managed the research project. M Ohta, M Nakataki, S Numata, T Tominaga, N Kameoka, H Kubo, and M Kinoshita recruited patients and discussed the results. T Takeda and K Matsuura conducted psychological examinations. M Otomo, N Takeichi, and M Harada performed fMRI. M Ohta and T Takeda organized the data. M Ohta, M Nakataki, and T Takeda searched the literature. M Ohta analyzed the data and wrote the first draft of this manuscript. M Nakataki and T Ohmori supervised data analysis and revised the manuscript. All authors read and approved the final manuscript. All authors contributed toward data analysis, drafting, and revising the paper and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.